Citrate

Citrate
Names


IUPAC name 2-hydroxypropane-1,2,3-tricarboxylate
Identifiers
ChemSpider	29081^Y
InChI InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/p-3^Y Key: KRKNYBCHXYNGOX-UHFFFAOYSA-K^Y
Jmol-3D images	Image
PubChem	31348
SMILES C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O
Properties
Chemical formula	C 6H 5O3− 7
Molar mass	189 g mol⁻¹
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

A citrate is a derivative of citric acid; that is, the salts, esters, and the polyatomic anion found in solution. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate. When part of a salt, the formula of the citrate ion is written as C₆H₅O₇³⁻ or C₃H₅O(COO)₃³⁻.

Other citric acid ions

Since citric acid is a multifunctional acid, intermediate ions exist, hydrogen citrate ion, HC₆H₅O₇²⁻ and dihydrogen citrate ion, H₂C₆H₅O₇⁻. These may form salts as well, called acid salts.

Acidity

Salts of the hydrogen citrate ions are weakly acidic, while salts of the citrate ion itself (with an inert cation such as sodium ion) are weakly basic.

Buffering

As a weak acid, citrate can be used as a component in buffer solutions, including the commonly used SSC 20X hybridization buffer.^[1] This buffer uses sodium citrate and sodium chloride to maintain a neutral 7.0 pH. Other buffers may use a mixture of sodium citrate and citric acid – canonical buffer tables compiled for biochemical studies^[2] describe solutions of citrate and acid for buffer pHs of between 3.0 and 6.2.

Chelating

Citric acid can act as a mild chelating agent; citrate, usually in the form of trisodium citrate, may be given as an anticoagulant, because it chelates calcium ions, and therefore inhibits coagulation. Another application is in the form of iron(II) citrate as a nutritional supplement. Here, the benefit is the solubility as a chelate of the otherwise mostly insoluble iron.

Metabolism

Citrate is an intermediate in the TCA (Krebs) cycle, a central metabolic pathway for both eukaryotes such as animals and plants and prokaryotes such as bacteria. After the pyruvate dehydrogenase complex forms acetyl-CoA, from pyruvate and five cofactors (thiamine pyrophosphate, lipoamide, FAD, NAD⁺, and CoA), citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate continues in the TCA cycle via aconitase with the eventual regeneration of oxaloacetate, which can combine with another molecule of acetyl CoA and continue cycling.

Some bacteria, notably E. coli, can produce and consume citrate internally as part of their TCA cycle, but are unable to use it as food because they lack the enzymes required to import it into the cell. The acquisition by these bacteria, after tens of thousands of generations, of the ability to use citrate as food was studied by Lenski et al.^[3]^[4] to explore mechanisms of evolution under selective pressure (in this case, a citrate-containing culture medium with limited amounts of other foods). They found evidence that in this case the innovation occurred via an accumulation of several somewhat rare mutations, none of which by itself would confer the selective advantage, rather than by a single extremely rare mutation.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

[[File:

[[<div style="display:block; width:30.1834671470831px; height:0px; overflow:hidden; position:relative; left:374.23731182425786px; top:602.398967699498px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:30.9999999999983px; height:0px; overflow:hidden; position:relative; left:466.4486251180706px; top:631.168519171318px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:29.1504661757638px; height:0px; overflow:hidden; position:relative; left:816.8495338242362px; top:541.621487793808px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:41.841620626151px; height:0px; overflow:hidden; position:relative; left:649.9875435628912px; top:278.04945206398px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:33.7681761528873px; height:0px; overflow:hidden; position:relative; left:330.70153294231534px; top:297.610619807187px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:32.582089552239px; height:0px; overflow:hidden; position:relative; left:177.09689795536426px; top:425.87537485759px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:68.73658375472704px; top:538.689173119075px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:88px; height:0px; overflow:hidden; position:relative; left:715.2163009404388px; top:401px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:80px; height:0px; overflow:hidden; position:relative; left:503.0px; top:670.5px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:84.9238578680197px; height:0px; overflow:hidden; position:relative; left:692.0761421319803px; top:573.5px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:304.2323578810314px; top:716.549820282624px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:33.621221037988px; height:0px; overflow:hidden; position:relative; left:367.5646397813722px; top:175.627991937516px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:720.2375300176794px; top:702.001875326864px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:720.2375300176792px; top:682.337193696082px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:73.3148283021269px; height:0px; overflow:hidden; position:relative; left:258.0px; top:207.5px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:853.3602503491594px; top:486.042093313318px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:853.3602503491594px; top:466.042093313318px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:304.2323578810314px; top:696.549820282624px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:68.73658375472704px; top:498.689173119076px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:48.2984700306043px; height:0px; overflow:hidden; position:relative; left:180.0px; top:310.519900497513px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:853.3602503491594px; top:506.042093313318px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:720.2375300176792px; top:662.337193696082px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:70px; height:0px; overflow:hidden; position:relative; left:216.0px; top:374.674493554328px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:82px; height:0px; overflow:hidden; position:relative; left:264.0px; top:272.330227037402px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:61.4143272597748px; height:0px; overflow:hidden; position:relative; left:221.89453081488801px; top:475.826018808777px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:68.73658375472704px; top:558.689173119075px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:52.4198466377163px; height:0px; overflow:hidden; position:relative; left:487.5801533622837px; top:199.5px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:47.2000923036619px; height:0px; overflow:hidden; position:relative; left:664.7999076963381px; top:198.406955168477px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:66px; height:0px; overflow:hidden; position:relative; left:277.0px; top:578px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:60px; height:0px; overflow:hidden; position:relative; left:68.73658375472704px; top:518.689173119076px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:174.797362167969px; height:0px; overflow:hidden; position:relative; left:111.0px; top:654.04700332349px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:154.310540655952px; height:0px; overflow:hidden; position:relative; left:575.6894593440477px; top:135.269018473869px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:170px; height:0px; overflow:hidden; position:relative; left:152.0px; top:124.074190177638px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:76px; height:0px; overflow:hidden; position:relative; left:682.0px; top:308.556556257706px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:46.2956622035883px; height:0px; overflow:hidden; position:relative; left:808.7043377964117px; top:363.951733482022px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:39px; height:0px; overflow:hidden; position:relative; left:813.9382716049388px; top:422.40772328832px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:36.5px; height:0px; overflow:hidden; position:relative; left:775.7640561670411px; top:541.621487793808px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:44.2885215390222px; height:0px; overflow:hidden; position:relative; left:670.9877017410322px; top:485.86403074685px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:41.8532982134678px; height:0px; overflow:hidden; position:relative; left:681.1902406172646px; top:427.288869264805px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:42.6019239578559px; height:0px; overflow:hidden; position:relative; left:692.5039932478962px; top:536.621487793808px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:28.5478699038022px; height:0px; overflow:hidden; position:relative; left:677.2474233020198px; top:598.540271103061px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:31.2611679545706px; height:0px; overflow:hidden; position:relative; left:642.4000247852737px; top:598.540271103061px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:32.9824561403508px; height:0px; overflow:hidden; position:relative; left:630.1160862354895px; top:693.89597205691px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:30.9999999999982px; height:0px; overflow:hidden; position:relative; left:466.4486251180698px; top:616.797517039126px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:30.1834671470831px; height:0px; overflow:hidden; position:relative; left:374.23731182425786px; top:588.027965567302px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:29.6136269214791px; height:0px; overflow:hidden; position:relative; left:289.5220258089487px; top:624.295539263445px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:70.9637798844278px; height:0px; overflow:hidden; position:relative; left:302.78215871956456px; top:542.264367816092px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:71.0094500492967px; height:0px; overflow:hidden; position:relative; left:302.75932363713014px; top:493.666666666667px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:39.3831123868514px; height:0px; overflow:hidden; position:relative; left:278.6168876131486px; top:422.876981279349px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:29.7294003600621px; height:0px; overflow:hidden; position:relative; left:203.66666666666663px; top:343.688918684141px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:35.0113378684808px; height:0px; overflow:hidden; position:relative; left:290.45787084901383px; top:243.69018283712px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:28.2086167800452px; height:0px; overflow:hidden; position:relative; left:454.45588384607703px; top:173.001159642582px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:151px; height:0px; overflow:hidden; position:relative; left:103.0px; top:152.25px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:183px; height:0px; overflow:hidden; position:relative; left:310.0px; top:92px; background:transparent; border-top:3px green solid"></div>]]

[[<div style="display:block; width:29.2970776041057px; height:0px; overflow:hidden; position:relative; left:659.0px; top:536.621487793808px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:27.0336779387258px; height:0px; overflow:hidden; position:relative; left:599.0px; top:693.89597205691px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:19.5546565671207px; height:0px; overflow:hidden; position:relative; left:466.350105337641px; top:690.298609635293px; background:transparent; border-top:3px blue solid"></div>]]

[[<div style="display:block; width:41.841620626151px; height:0px; overflow:hidden; position:relative; left:780.9875435628912px; top:330.04945206398px; background:transparent; border-top:3px blue solid"></div>]]

[[

]]

|{{{bSize}}}px|alt=TCA Cycle edit|]]

TCA Cycle edit

↑ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".

Fatty acid synthesis

Citrate can also be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis and into oxaloacetate. Citrate is a positive modulator of this conversion, and allosterically regulates the enzyme acetyl-CoA carboxylase, which is the regulating enzyme in the conversion of acetyl-CoA into malonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported to the cytoplasm, converted to acetyl CoA, which is converted into malonyl CoA by the acetyl CoA carboxylase, which is allosterically modulated by citrate.

See also TCA cycle

Role in glycolysis

High concentrations of cytosolic citrate can inhibit phosphofructokinase, catalyst of one of the rate-limiting steps of glycolysis.

References

↑ Maniatis, T.; Fritsch, E. F.; Sambrook, J. 1982. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
↑ Gomori, G. (1955). "Methods in Enzymology Volume 1". Methods in Enzymology 1. p. 138. doi:10.1016/0076-6879(55)01020-3. ISBN 9780121818012. |chapter= ignored (help)
↑ http://phys.org/news/2014-02-bacteria-freezer-yield-startling-results.html
↑ http://www.rpgroup.caltech.edu/courses/Evolution_GIST_2013/files_2013/articles/PNAS-2008-Blount-7899-906.pdf

Citric Acid Cycle Metabolic Pathway

Acetyl-CoA

NADH + H⁺

NAD⁺

H₂O

FADH₂

FAD

CoA + ATP(GTP)

P_i + ADP(GDP)

H₂O

NADH + H⁺ + CO₂

CoA

NAD⁺

H₂O

NAD(P)⁺

NAD(P)H + H⁺

CO₂

cis-Aconitate

Index of inborn errors of metabolism

Description	Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates

Disorders	Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs

Treatment	Drugs other

Amino acid metabolism metabolic intermediates

K→acetyl-CoA

lysine→	Saccharopine Allysine α-Aminoadipic acid α-Ketoadipate Glutaryl-CoA Glutaconyl-CoA Crotonyl-CoA β-Hydroxybutyryl-CoA

leucine→	α-Ketoisocaproic acid Isovaleryl-CoA 3-Methylcrotonyl-CoA 3-Methylglutaconyl-CoA HMG-CoA

tryptophan→alanine→	N'-Formylkynurenine Kynurenine Anthranilic acid 3-Hydroxykynurenine 3-Hydroxyanthranilic acid 2-Amino-3-carboxymuconic semialdehyde 2-Aminomuconic semialdehyde 2-Aminomuconic acid Glutaryl-CoA

G→pyruvate→citrate

glycine→serine→	3-Phosphoglyceric acid glycine→creatine: Glycocyamine Phosphocreatine Creatinine

G→glutamate→
α-ketoglutarate

histidine→	Urocanic acid Imidazol-4-one-5-propionic acid Formiminoglutamic acid Glutamate-1-semialdehyde

proline→	1-Pyrroline-5-carboxylic acid

arginine→	Agmatine Ornithine Cadaverine Putrescine

other	cysteine+glutamate→glutathione: γ-Glutamylcysteine

G→propionyl-CoA→
succinyl-CoA

valine→	α-Ketoisovaleric acid Isobutyryl-CoA Methacrylyl-CoA 3-Hydroxyisobutyryl-CoA 3-Hydroxyisobutyric acid 2-Methyl-3-oxopropanoic acid

isoleucine→	2,3-Dihydroxy-3-methylpentanoic acid 2-Methylbutyryl-CoA Tiglyl-CoA 2-Methylacetoacetyl-CoA

methionine→	generation of homocysteine: S-Adenosyl methionine S-Adenosyl-L-homocysteine Homocysteine conversion to cysteine: Cystathionine alpha-Ketobutyric acid+Cysteine

threonine→	α-Ketobutyric acid

propionyl-CoA→	Methylmalonyl-CoA

G→fumarate

phenylalanine→tyrosine→	4-Hydroxyphenylpyruvic acid Homogentisic acid 4-Maleylacetoacetic acid

G→oxaloacetate

see urea cycle

Other

Cysteine metabolism	Cysteine sulfinic acid

Index of inborn errors of metabolism

Description	Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates

Disorders	Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs

Treatment	Drugs other

Index of biochemical families

Carbohydrates	Alcohols Glycoproteins Glycosides

Lipids	Eicosanoids Fatty acids intermediates Glycerides Phospholipids Sphingolipids Steroids

Nucleic acids	Constituents intermediates

Proteins	Amino acids intermediates

Other	Tetrapyrroles intermediates

Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)

Antiplatelet drugs

Glycoprotein IIb/IIIa inhibitors	Abciximab Eptifibatide Tirofiban Roxifiban Orbofiban

ADP receptor/P2Y₁₂ inhibitors	Thienopyridines Clopidogrel Prasugrel Ticlopidine Nucleotide/nucleoside analogs Cangrelor Elinogrel Ticagrelor

Prostaglandin analogue (PGI2)	Beraprost Iloprost Prostacyclin Treprostinil

COX inhibitors	Acetylsalicylic acid/Aspirin^# Aloxiprin Carbasalate calcium Indobufen Triflusal

Thromboxane inhibitors	Thromboxane synthase inhibitors Dipyridamole (+Aspirin) Picotamide Receptor antagonists Terutroban^†

Phosphodiesterase inhibitors	Cilostazol Dipyridamole Triflusal

Other	Cloricromen Ditazole Vorapaxar

Anticoagulants

Vitamin K antagonists
(inhibit II, VII, IX, X)

Factor Xa inhibitors
(with some II inhibition)

Heparin group/ glycosaminoglycans/ (bind antithrombin)	Low molecular weight heparin Bemiparin Certoparin Dalteparin Enoxaparin Nadroparin Parnaparin Reviparin Tinzaparin^‡ Oligosaccharides Fondaparinux Idraparinux^§ Heparinoids Danaparoid Dermatan sulfate Sulodexide

Direct Xa inhibitors	Xabans Apixaban Betrixaban^§ Darexaban^§ Edoxaban Otamixaban^§ Rivaroxaban

Direct thrombin (IIa) inhibitors

Bivalent: Hirudin
- Bivalirudin
- Desirudin
- Lepirudin
Univalent: Argatroban
Dabigatran
Melagatran^‡
Ximelagatran^‡

Other

Thrombolytic drugs/
fibrinolytics

Non-medicinal

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Index of cells from bone marrow

Description	Immune system Cells Physiology coagulation proteins granule contents colony-stimulating heme and porphyrin metabolism intermediates

Disease	Red blood cell Monocyte and granulocyte Neoplasms and cancer Histiocytosis Symptoms and signs eponymous Blood tests findings

Treatment	Transfusion Drugs thrombosis bleeding other